3639 Background: Apoptosis is a programmed cell death mechanism where cells respond to internal or external stimuli by initiating a cascade of events and enzymes leading to cell death. One of the hallmarks of cancer is the ability of tumor cells to resist these apoptotic stimuli. This allows tumor cells to have aberrant metabolisms, such as sphingolipid metabolism in tumor cell lysosomes, or mutations which would normally commit cells to death. Saposin C, the protein component of BXQ-350, Bexion Pharmaceuticals’ proprietary biotherapeutic, is involved in normal lysosomal sphingolipid metabolism. Removing resistance, shortcutting steps leading to apoptosis, or correcting sphingolipid metabolism can result in the death of these tumor cells. Methods: The GBM cell line Gli36ΔEGFR was plated in 96 well plates at a density of 1x104 cells per well in Dulbecco’s Modified Eagle Media with 10% FBS overnight at 37oC for caspase and cytotoxicity assays. Cells were treated with 9uM to 30uM BXQ-350 in triplicate and incubated for 24 hours at 37oC. Promega’s Caspase-Glo 9 or Caspase-Glo 3/7 reagent was added to appropriate wells and the plates were incubated at room temperature in the dark for 3 hours then luminescence was read. The parallel cytotoxic assay was run under the same conditions except Roche’s MTT labeling reagent was added to the appropriate wells after 24 hours and incubated at 370C for 4 hours. Solubilization solution was added to each well and the plate was incubated at 37oC overnight then absorbance was read. The GBM cell line U87 MG was used to determine lysosomal targeting. U87 MG cells were treated with 10uM BXQ-350 and incubated at 37oC overnight. They were stained with anti-SapC (RFP) and anti-LAMP1 (GFP) antibodies and images were taken. Results: BXQ-350 mediated cell death is correlated with a rise in Caspase 3, Caspase 7 and Caspase 9 activity. The caspase activity levels did not rise until after BXQ-350 passed its IC50 and stayed elevated. Caspases 3/7 levels showed higher activity compared to untreated than Caspase 9. In addition to this, BXQ-350 was seen to colocalize to LAMP1, a lysosomal membrane protein. Conclusions: BXQ-350 tracks to the lysosomal membrane where it initiates the cascade of enzymes necessary to cause apoptosis. Caspases 3/7 are the effector caspases and are necessary for the completion of the apoptotic pathway. The higher activity levels of these caspases show the cells are committed to cell death not allowing these cells to subvert apoptosis. This removes one of the major barriers to fighting cancer.